一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Antiviral research >>article
Antiviral research

Antiviral research

IF: 4.5
Download PDF

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors

Published:1 May 2022 DOI: 10.1016/j.antiviral.2022.105272 PMID: 35278581
K.Y. Chen , T. Krischuns , L. Ortega Varga , E. Harigua-Souiai , S. Paisant , A. Zettor , J. Chiaravalli , A. Delpal , D. Courtney , A. O'Brien , S.C. Baker , E. Decroly , C. Isel , F. Agou , Y. Jacob , A. Blondel , N. Naffakh

Abstract

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4–8?μM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
PACRITINIB |CAS 937272-79-2 937272-79-2 C28H32N4O3 171 suppliers $18.00-$8950.00
PACRITINIB |CAS 937272-79-2 937272-79-2 C28H32N4O3 171 suppliers $18.00-$8950.00
PACRITINIB |CAS 937272-79-2 937272-79-2 C28H32N4O3 171 suppliers $18.00-$8950.00
PACRITINIB |CAS 937272-79-2 937272-79-2 C28H32N4O3 171 suppliers $18.00-$8950.00
陆丰市| 青田县| 平果县| 巨鹿县| 教育| 乌鲁木齐县| 黔西县| 垫江县| 集安市| 确山县| 神池县| 洛川县| 体育| 凤冈县| 满城县| 子长县| 同仁县| 神木县| 扎鲁特旗| 灌南县| 肥东县| 关岭| 邳州市| 铜山县| 和静县| 龙州县| 云阳县| 冀州市| 通山县| 绿春县| 栾城县| 安徽省| 长垣县| 合山市| 读书| 永登县| 汶川县| 平塘县| 固原市| 天气| 栖霞市|